1. Field of the Invention
This invention relates to seventeen new compounds obtained from an acetone-extracted product of gamboge resin. The seventeen new compounds have been demonstrated to have activities in inhibiting the growth of tumor/cancer cells. Therefore, this invention also relates to the use of the seventeen new compounds in the preparation of pharmaceutical compositions.
2. Description of the Related Art
Gamboge resin is the gum-resin secreted by the plant of Garcinia sp. of the family Guttiferae. It has been used as a source of vegetative dyes and pigments since the old days. It is also used in folk medicine in some areas such as India and Thailand.
Garcinia (TENGHUANG in pinyin), which is commonly known as gamboge, is a kind of evergreen trees that grow in tropical regions. The main species grown in India is “Garcinia morella Desv,” whereas the main species grown in Thailand is “G. harburyi Hook f.” Before the flowering period, the bark of the tree is cut open in a spiral shape about 2 meters from the ground to collect the exuding resin. The resin is then subjected to heat-drying to result in a solidified gamboge resin.
According to traditional Chinese medicine (TCM), gamboge is effective in combating inflammations, clearing away toxins, stopping blood bleeding, and killing worms. Ever since 1934, there have been a number of reports on the components of the gamboge resin. At present, it is known that many compounds can be isolated from extracts of gamboge resin, including: morellin, morellic acid, gambogic acid, morellinol, isomorellin, isomorellic acid, isogambogic acid, isomorellinol, neogambogic acid, desoxymorellin, dihydroisomorellin, α-guttiferin, β-guttiferin, gambogenic acid, desoxygambogenin, gambogellic acid, epigambogic acid, epiisogambogic acid, isogambogenic acid, 30-hydroxygambogic acid, etc.
Some studies have reported the cytotoxic activity of certain components of gamboge resin on human cervical cancer cells HeLa, human nasopharyngeal cancer cells KB, human leukemia cells K562, and doxorubicin-resistant K562 cell lines, etc. (J. Asano et al. (1996), Phytochemistry, 41:815-820; L. J. Lin et al. (1993), Magnetic Resonance in Chemistry, 31:340-347; Q. B. Han et al. (2006), Planta Med., 72:281-284; Q. B. Han et al. (2006), Chem. Pharm. Bull., 54:265-267; Q. B. Han et al. (2006), Chemistry & Biodiversity, 3:101-105).
U.S. Pat. No. 6,462,041 B1 has disclosed gambogic acid and its analogs and derivatives as represented by the following Formulae I, II and III:
                wherein a dash line denotes a single bond, a double bond, or an epoxy group; and X, Y, and R1 to R3 have the definitions as disclosed in said US patent.        
Compounds having one of the aforesaid Formulae I-III are disclosed to be activators of caspases and inducers of apoptosis. However, U.S. Pat. No. 6,462,041 B1 has disclosed neither a compound of Formula I that has a 32,33-epoxy group, nor a process for preparing the same.
In Acta Chimica Sinica, 2008, 66(22):2513-2517, Ming-Meia Jia et al., studied the chemical components of Garcinia hanburyi and isolated fifteen compounds from the cold ethanol-extracted product of Garcinia hanburyi via silica gel column chromatography (gradient elution solvent system: petroleum ether-acetone, acetone, methanol) and preparative HPLC. According to structure identification, the fifteen compounds were identified as 2α-hydroxy-3β-acetoxy-lup-20(29)-en-28-oic acid (1), 10α-hydroxyepigambogic acid (2), gambogic acid (3), isogambogic acid (4), gambogin (5), gambogoic acid B (6), desoxymorellin (7), isomorellin (8), gambogenic acid (9), isogambogenin (10), gambogellic acid (11), desoxygambogenin (12), morellic acid (13), isomorellic acid (14), and 30-hydroxygambogic acid (15).
U.S. Pat. No. 7,138,428 B2 (corresponding to TW I282280 and CN 100413868 C) has disclosed an acetone-extracted product from gamboge resin, i.e., TSB-14. In addition, nine compounds were further purified from said acetone-extracted product TSB-14, including a new compound formoxanthone A, and eight known compounds betulin, betulinic acid, morellic acid, isomorellic acid, gambogic acid, isogambogic acid, isomorellinol and desoxymorellin.
The acetone-extracted product TSB-14 and the nine purified compounds have been demonstrated to have effects in inhibiting the growth of tumor/cancer cells such as liver cancer cells (HepG2), lung cancer cells (A549), breast cancer cells (MCF-7), colon cancer cells (HT-29), leukemia cells (HL-60), and lymphoma cancer cells (U937).
US 2007/0093456 A1 has disclosed a derivative of gambogic acid, which is identified as “methyl 37,38-dihydroxy-gambogate” and has the following chemical structure:

It has been found from experiments that methyl 37,38-dihydroxy-gambogate can act as an activator of caspases and an inducer of apoptosis.
In Journal of Natural Products (2009), 72:117-124, S. J. Tao et al. reported that twelve new xanthones (such as oxygambogic acid shown below, methyl 8,8a-dihydromorellate, 7-methoxygambogellic acid, etc.) and a pair of new natural products (i.e., 8,8a-dihydro-8-hydroxygambogic acid and its isomer) were isolated from the resin of G. hanbury.

The stereostructure of oxygambogic acid has yet to be confirmed since the configuration of the C15/C16 double bond could not be determined due to the overlapping of the H-15 and H-16 signals in the 1H-NMR spectral data. S. J. Tao et al. further found from pharmacological experiments that in addition to methyl 8,8a-dihydromorellate, all of the other tested thirteen compounds were effective in inhibiting the growth of HeLa cancer cells.
In addition to the activities in inhibiting the growth of tumor/cancer cells, the extracts of gamboge resin have been demonstrated to have other biological activities. For instance, in the report of A. Panthong et al. Journal of Ethnopharmacology (2007), 111:335-340, an ethyl acetate extract obtained from the resin of G. hanburyi Hook f. and named GH5763 was demonstrated to exhibit anti-inflammatory, analgesic and antipyretic activities.
Despite the aforesaid, there still exists a need for medicinal chemists and pharmaceutical manufacturers in the pharmaceutical industry to explore new compound(s) or new extract(s) that can be easily prepared and that exhibit desirable biological activities such as anti-cancer activity, analgesic activity, anti-inflammatory activity, etc.
Upon further investigation, the applicants have obtained seventeen new compounds from the acetone-extracted product TSB-14 of gamboge resin, in which the seventeen new compounds have been demonstrated to have anti-cancer activity.